{{Short description|Class of pharmacological agents}} {{Use dmy dates|date=March 2024}} {{Globalize|article|date=August 2025|the United States}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Human body weight}}
'''Anti-obesity medication''' or '''weight loss medications''' are pharmacological agents that reduce excess body fat and cause weight loss. These medications alter one of the fundamental processes of weight regulation, by: reducing appetite and consequently energy intake, increasing energy expenditure, redirecting nutrients from adipose to lean tissue, or interfering with the absorption of calories.<ref>{{cite journal |last1=Ryan |first1=Donna H. |title=Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice? |journal=Journal of Obesity & Metabolic Syndrome |date=September 2021 |volume=30 |issue=3 |pages=196–208 |doi=10.7570/jomes21033 |pmid=34518444 |pmc=8526285 |issn=2508-6235}}</ref><ref>{{cite journal |last1=Jimenez-Munoz |first1=Carlos M. |last2=López |first2=Marta |last3=Albericio |first3=Fernando |last4=Makowski |first4=Kamil |title=Targeting Energy Expenditure—Drugs for Obesity Treatment |journal=Pharmaceuticals |date=May 2021 |volume=14 |issue=5 |page=435 |doi=10.3390/ph14050435 |pmid=34066399 |pmc=8148206 |issn=1424-8247 |doi-access=free }}</ref><ref name=NICECG043>{{NICE|43|Obesity: The prevention, identification, assessment and management of overweight and obesity in adults and children|2006}}</ref>
Weight loss drugs have been developed since the early twentieth century, and many have been banned or withdrawn from the market due to adverse effects, including deaths; other drugs proved ineffective. Although many earlier drugs were stimulants such as amphetamines, in the early 2020s, GLP-1 receptor agonists became popular for weight loss.
As of 2023, the medications liraglutide, naltrexone/bupropion, orlistat, semaglutide, tirzepatide and phentermine/topiramate are approved by the US Food and Drug Administration (FDA) for weight management in combination with reduced-calorie diet and increased physical activity.<ref name="Elmaleh-Sachs 2023">{{cite journal |last1=Elmaleh-Sachs |first1=Arielle |last2=Schwartz |first2=Jessica L. |last3=Bramante |first3=Carolyn T. |last4=Nicklas |first4=Jacinda M. |last5=Gudzune |first5=Kimberly A. |last6=Jay |first6=Melanie |title=Obesity Management in Adults: A Review |journal=JAMA |date=28 November 2023 |volume=330 |issue=20 |pages=2000–2015 |doi=10.1001/jama.2023.19897|pmid=38015216 |pmc=11325826 }}</ref> Medications to treat obesity may be considered in those with a body mass index above 30, or above 27 with obesity related complications (such as hypertension, hyperlipidemia, cardiovascular disease, or obstructive sleep apnea).<ref name="Elmaleh-Sachs 2023" /> As of 2022, no medication has been shown to be as effective at long-term weight reduction as bariatric surgery.<ref name="pmid34815532" />
==Mechanisms of action==
===Energy intake=== * 5-HT<sub>2C</sub> receptor agonists reduce appetite by working on serotonin receptors in a region of the brain called the hypothalamus.<ref>{{cite journal |vauthors=Shukla AP, Kumar RB, Aronne LJ |date=2015 |title=Lorcaserin Hcl for the treatment of obesity |journal=Expert Opinion on Pharmacotherapy |volume=16 |issue=16 |pages=2531–2538 |doi=10.1517/14656566.2015.1096345 |pmid=26472579 |s2cid=44520532}}</ref> Lorcaserin (Belviq) was FDA approved for weight loss but was withdrawn from the market because a safety clinical trial shows an increased occurrence of cancer.<ref>{{cite web |date=19 February 2019 |title=FDA requests the withdrawal of the weight-loss drug Belviq, Belviq XR (lorcaserin) from the market |url=https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-requests-withdrawal-weight-loss-drug-belviq-belviq-xr-lorcaserin-market |url-status=live |archive-url=https://web.archive.org/web/20201220061627/https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-requests-withdrawal-weight-loss-drug-belviq-belviq-xr-lorcaserin-market#:~:text=On%20February%2013%2C%202020%20FDA,an%20increased%20occurrence%20of%20cancer |archive-date=20 December 2020 |access-date=23 December 2020 |website=U.S. Food and Drug Administration (FDA)}}</ref> *Cannabinoid receptor antagonists were developed to treat obesity because researchers noticed that cannabinoid agonists (such as THC, the main pharmacologically active component of cannabis), increased appetite. However, some drugs in this class such as rimonabant were withdrawn or ceased development due to concerns about mental health and suicide. More selective drugs—some are in development that act only in peripheral tissues, not the brain—may be able to achieve this result with fewer adverse effects.<ref>{{cite journal |last1=Rohbeck |first1=Elisabeth |last2=Eckel |first2=Juergen |last3=Romacho |first3=Tania |title=Cannabinoid Receptors in Metabolic Regulation and Diabetes |journal=Physiology |date=March 2021 |volume=36 |issue=2 |pages=102–113 |doi=10.1152/physiol.00029.2020 |pmid=33595385 |s2cid=231943477 |hdl=10835/20978 |hdl-access=free }}</ref><ref>{{cite journal |last1=Nguyen |first1=Thuy |last2=Thomas |first2=Brian F. |last3=Zhang |first3=Yanan |title=Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: current approaches for therapeutics development |journal=Current Topics in Medicinal Chemistry |date=2019 |volume=19 |issue=16 |pages=1418–1435 |doi=10.2174/1568026619666190708164841 |pmid=31284863 |pmc=6771026 |issn=1568-0266}}</ref> * GLP-1 agonists such as tirzepatide, semaglutide, and liraglutide slow gastric emptying and also have neurologically driven effects on appetite.<ref>{{cite journal | vauthors = Shah M, Vella A | title = Effects of GLP-1 on appetite and weight | journal = Reviews in Endocrine & Metabolic Disorders | volume = 15 | issue = 3 | pages = 181–187 | date = September 2014 | pmid = 24811133 | pmc = 4119845 | doi = 10.1007/s11154-014-9289-5 }}</ref> It is unknown if GLP-1 agonists or dual/triple agonists of GLP-1 and/or the glucagon or GIP receptors act solely by reducing energy intake or if they also increase energy expenditure.<ref name=Genchi/> *Setmelanotide is an agonist of the melanocortin 4 receptor and is used in people with certain rare genetic conditions that cause obesity. It is less effective and not approved for general obesity.<ref>{{cite journal |last1=Son |first1=Jang Won |last2=Kim |first2=Sungrae |title=Comprehensive Review of Current and Upcoming Anti-Obesity Drugs |journal=Diabetes & Metabolism Journal |date=December 2020 |volume=44 |issue=6 |pages=802–818 |doi=10.4093/dmj.2020.0258 |pmid=33389955 |pmc=7801751 | doi-access=free }}</ref>
===Energy expenditure=== *Adrenergic agonists that work on the beta-2 adrenergic receptor increase energy expenditure. Although some such as clenbuterol are used without medical approval for weight loss, none have achieved approval for this indication due to cardiac risks.<ref name=Christoffersen/><ref>{{cite journal |last1=Kumari |first1=Sweta |last2=Pal |first2=Biplab |last3=Sahu |first3=Sanjeev Kumar |last4=Prabhakar |first4=Pranav Kumar |last5=Tewari |first5=Devesh |title=Adverse events of clenbuterol among athletes: a systematic review of case reports and case series |journal=International Journal of Legal Medicine |date=July 2023 |volume=137 |issue=4 |pages=1023–1037 |doi=10.1007/s00414-023-02996-1 |pmid=37062796 |s2cid=258178293 }}</ref> The anti-obesity effects of amphetamines, besides acting on the brain to reduce energy intake, are also mediated by the beta-2 adrenergic receptor.<ref>{{cite journal |last1=Morris |first1=Alan |title=Unravelling novel weight loss mechanisms |journal=Nature Reviews Endocrinology |date=July 2020 |volume=16 |issue=7 |page=343 |doi=10.1038/s41574-020-0374-4 |pmid=32461617 |s2cid=218913041 |issn=1759-5037|doi-access=free }}</ref><ref name="ncbi.nlm.nih.gov">{{cite journal |last1=Coulter |first1=Ann A. |last2=Rebello |first2=Candida J. |last3=Greenway |first3=Frank L. |title=Centrally Acting Drugs for Obesity: Past, Present, andFuture |journal=Drugs |date=July 2018 |volume=78 |issue=11 |pages=1113–1132 |doi=10.1007/s40265-018-0946-y |pmid=30014268 |pmc=6095132 |issn=0012-6667}}</ref> Ephedrine (and related compounds that are also active ingredients in ephedra preparations) exert their effects by acting directly and indirectly as adrenergic agonists.<ref>{{cite journal |last1=Munafò |first1=Antonio |last2=Frara |first2=Stefano |last3=Perico |first3=Norberto |last4=Di Mauro |first4=Rosaria |last5=Cortinovis |first5=Monica |last6=Burgaletto |first6=Chiara |last7=Cantarella |first7=Giuseppina |last8=Remuzzi |first8=Giuseppe |last9=Giustina |first9=Andrea |last10=Bernardini |first10=Renato |title=In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine |journal=Reviews in Endocrine and Metabolic Disorders |date=December 2021 |volume=22 |issue=4 |pages=1013–1025 |doi=10.1007/s11154-021-09658-w |pmid=33945051 |pmc=8724077 |issn=1573-2606}}</ref> *The discontinued drug 2,4-dinitrophenol works by increasing energy expenditure by decreasing the efficiency of mitochondria (uncoupling agent).<ref name=Christoffersen/> A prodrug of DNP, HU6, has been tested in clinical trials for weight loss and fatty liver disease.<ref>{{cite journal |last1=Harrison |first1=Stephen A. |last2=Loomba |first2=Rohit |last3=Dubourg |first3=Julie |last4=Ratziu |first4=Vlad |last5=Noureddin |first5=Mazen |title=Clinical Trial Landscape in NASH |journal=Clinical Gastroenterology and Hepatology |date=July 2023 |volume=21 |issue=8 |pages=2001–2014 |doi=10.1016/j.cgh.2023.03.041|pmid=37059159 |s2cid=258115543 }}</ref> *Fibroblast growth factor-21 receptor agonists and drugs increasing FGF-21 activity are being investigated for obesity-related diseases; they can increase energy expenditure and several have been tested in humans.<ref>{{cite journal |last1=Sonoda |first1=Junichiro |last2=Chen |first2=Mark Z. |last3=Baruch |first3=Amos |title=FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases |journal=Hormone Molecular Biology and Clinical Investigation |date=May 2017 |volume=30 |issue=2 |article-number=20170002 |doi=10.1515/hmbci-2017-0002 |pmid=28525362 |s2cid=4420935 |issn=1868-1891|doi-access=free }}</ref><ref>{{cite journal |last1=Abdi Beshir |first1=Semira |last2=Ahmed Elnour |first2=Asim |last3=Soorya |first3=Aadith |last4=Parveen Mohamed |first4=Affana |last5=Sir Loon Goh |first5=Sheron |last6=Hussain |first6=Nadia |last7=Al Haddad |first7=Amal H. I. |last8=Hussain |first8=Faizah |last9=Yousif Khidir |first9=Israa |last10=Abdelnassir |first10=Zainab |title=A narrative review of approved and emerging anti-obesity medications |journal=Saudi Pharmaceutical Journal |date=October 2023 |volume=31 |issue=10 |article-number=101757 |doi=10.1016/j.jsps.2023.101757 |pmid=37712012 |pmc=10497995 |issn=1319-0164}}</ref> *Thyroid hormones, another early weight loss drug, also raised energy expenditure but ceased to be used for weight loss due to cardiac risks and other adverse effects.<ref name=Christoffersen>{{cite journal |last1=Christoffersen |first1=Berit Østergaard |last2=Sanchez-Delgado |first2=Guillermo |last3=John |first3=Linu Mary |last4=Ryan |first4=Donna H. |last5=Raun |first5=Kirsten |last6=Ravussin |first6=Eric |title=Beyond appetite regulation: Targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss |journal=Obesity |date=April 2022 |volume=30 |issue=4 |pages=841–857 |doi=10.1002/oby.23374 |pmid=35333444 |pmc=9310705 |issn=1930-7381}}</ref> Selective thyromimetics that work on the thyroid hormone receptor beta may be able to exert some of the beneficial thermogenic effects of thyroid hormones with fewer adverse effects, but none have received approval as of 2023.<ref name=Genchi>{{cite journal | vauthors = Genchi VA, Palma G, Sorice GP, D'Oria R, Caccioppoli C, Marrano N, Biondi G, Caruso I, Cignarelli A, Natalicchio A, Laviola L, Giorgino F, Perrini S |title=Pharmacological modulation of adaptive thermogenesis: new clues for obesity management? |journal=Journal of Endocrinological Investigation |date=November 2023 |volume=46 |issue=11 |pages=2213–2236 |doi=10.1007/s40618-023-02125-0 |pmid=37378828 |pmc=10558388 |issn=1720-8386}}</ref>
===Both=== *Amylin analogues can both reduce energy intake and increase expenditure and can usefully be combined with leptin analogues for synergistic effect.<ref>{{cite journal |last1=Lutz |first1=T. A. |title=Gut hormones such as amylin and GLP-1 in the control of eating and energy expenditure |journal=International Journal of Obesity Supplements |date=December 2016 |volume=6 |issue=1 |pages=S15–S21 |doi=10.1038/ijosup.2016.4 |pmid=28685025 |pmc=5485879 |issn=2046-2174}}</ref><ref>{{cite journal |last1=Mietlicki-Baase |first1=Elizabeth G. |title=Amylin-mediated control of glycemia, energy balance, and cognition |journal=Physiology & Behavior |date=August 2016 |volume=162 |pages=130–140 |doi=10.1016/j.physbeh.2016.02.034 |pmid=26922873 |pmc=4899204 |issn=0031-9384}}</ref> The dual amylin and calcitonin receptor agonist cagrilintide, in combination with semaglutide, was more effective than semaglutide alone in promoting weight loss in clinical trials.<ref name="dom-pubs.onlinelibrary.wiley.com">{{cite journal |last1=Idris |first1=Iskandar |title=Coadministration of the long-acting amylin analog cagrilintide plus semaglutide ( CagriSema ), resulted in significantly greater weight loss, along with improved measures of glucose control, in a short phase 2 trial of patients with type 2 diabetes |journal=Diabetes, Obesity and Metabolism Now |date=July 2023 |volume=1 |issue=7 |article-number=e68 |doi=10.1002/doi2.68 |s2cid=260221980 |issn=2688-8939|doi-access=free }}</ref><ref>{{cite journal |last1=Holst |first1=Jens Juul |last2=Jepsen |first2=Sara Lind |last3=Modvig |first3=Ida |title=GLP-1 – Incretin and pleiotropic hormone with pharmacotherapy potential. Increasing secretion of endogenous GLP-1 for diabetes and obesity therapy |journal=Current Opinion in Pharmacology |date=April 2022 |volume=63 |article-number=102189 |doi=10.1016/j.coph.2022.102189|pmid=35231672 |s2cid=247153792 |doi-access=free }}</ref> *Glucagon receptor agonists both reduce energy intake and increase energy expenditure in humans. They can cause hyperglycemia so it is recommended to combine them with a hypoglycemic drug, such as a GLP-1 or GIP receptor agonist.<ref>{{cite journal |last1=Conceição-Furber |first1=Ellen |last2=Coskun |first2=Tamer |last3=Sloop |first3=Kyle W. |last4=Samms |first4=Ricardo J. |title=Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity? |journal=Frontiers in Endocrinology |date=April 2022 |volume=13 |article-number=868037 |doi=10.3389/fendo.2022.868037 |pmid=35547006 |pmc=9081793 |issn=1664-2392 |doi-access=free }}</ref><ref>{{cite journal |last1=Novikoff |first1=Aaron |last2=Müller |first2=Timo D. |title=The molecular pharmacology of glucagon agonists in diabetes and obesity |journal=Peptides |date=July 2023 |volume=165 |article-number=171003 |doi=10.1016/j.peptides.2023.171003 |pmid=36997003 |pmc=10265134 |issn=0196-9781}}</ref>
===Other mechanisms=== *Bimagrumab, an experimental drug, works by inhibiting the action of myostatin, which limits the size of skeletal muscle. The drug has shown the ability to increase lean mass simultaneously to decreasing fat mass in obese humans, which is beneficial because it preserves or increases energy expenditure while reducing risks associated with excess fat.<ref name=Christoffersen/> *Orlistat (Xenical) and cetilistat are lipase inhibitors that reduce intestinal fat absorption by inhibiting pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. Without this enzyme, triglycerides from the diet are prevented from being hydrolyzed into absorbable free fatty acids and are excreted undigested.<ref>{{cite journal | vauthors = Yamada Y, Kato T, Ogino H, Ashina S, Kato K | title = Cetilistat (ATL-962), a novel pancreatic lipase inhibitor, ameliorates body weight gain and improves lipid profiles in rats | journal = Hormone and Metabolic Research | volume = 40 | issue = 8 | pages = 539–543 | date = August 2008 | pmid = 18500680 | doi = 10.1055/s-2008-1076699 | s2cid = 29076657 }}</ref> Frequent oily bowel movements steatorrhea is a possible side effect of using orlistat. Originally available only by prescription, it was approved by the FDA for over-the-counter sale in February 2007.<ref>{{cite web | title=Orlistat (marketed as Alli and Xenical) Information | website=U.S. Food and Drug Administration | date=8 July 2015 | url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/orlistat-marketed-alli-and-xenical-information | archive-url=https://web.archive.org/web/20191213203614/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/orlistat-marketed-alli-and-xenical-information | archive-date=13 December 2019 | access-date=14 January 2024}}</ref> *SGLT2 inhibitors cause the loss of {{convert|60–100|g}} glucose in the urine each day and are associated with a modest, sustained weight loss of {{convert|1.5-2|kg}} in people with type 2 diabetes. The weight loss is less than expected due to compensatory increases in energy intake, but is additive when combined with GLP-1 receptor agonists.<ref>{{cite journal |last1=Pereira |first1=Maria J. |last2=Eriksson |first2=Jan W. |title=Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity |journal=Drugs |date=2019 |volume=79 |issue=3 |pages=219–230 |doi=10.1007/s40265-019-1057-0 |pmid=30701480 |pmc=6394798 |issn=0012-6667 |doi-access=free }}</ref>
==History== The first described attempts at producing weight loss are those of Soranus of Ephesus, a Greek physician, in the second century AD. He prescribed elixirs of laxatives and purgatives, as well as heat, massage, and exercise. This remained the mainstay of treatment for well over a thousand years. It was not until the 1920s and 1930s that new treatments began to appear. Based on its effectiveness for hypothyroidism, thyroid hormone became a popular treatment for obesity in euthyroid people. It had a modest effect but produced the symptoms of hyperthyroidism as a side effect, such as palpitations and difficulty sleeping.<ref name="pmid4610359">{{cite journal | vauthors = Parascandola J | title = Dinitrophenol and bioenergetics: an historical perspective | journal = Molecular and Cellular Biochemistry | volume = 5 | issue = 1–2 | pages = 69–77 | date = November 1974 | pmid = 4610359 | doi = 10.1007/BF01874175 | s2cid = 2656970 }}</ref> 2,4-Dinitrophenol (DNP) was introduced in 1933; this worked by uncoupling the biological process of oxidative phosphorylation in mitochondria, causing them to produce heat instead of ATP. Overdose caused fatal hyperthermia and DNP also caused cataracts in some users. After the passage of the Food, Drug, and Cosmetic Act in 1938, the FDA banned DNP for human consumption.<ref name=Swann>{{cite book |last1=Swann |first1=John P. |title=Perspectives on Twentieth-century Pharmaceuticals |date=2010 |publisher=Peter Lang |isbn=978-3-03910-920-3 |pages=289, 292, 299, 301 |chapter=Reducing with dinitrophenol : self-medication, and the challenge of regulating a dangerous pharmaceutical before the US Food, Drug, and Cosmetic Act}}</ref>
Amphetamines (marketed as Benzedrine) became popular for weight loss during the late 1930s. They worked primarily by suppressing appetite, and had other beneficial effects such as increased alertness. Use of amphetamines increased over the subsequent decades, including Obetrol and culminating in the "rainbow diet pill" regime.<ref name="AJPH2012">{{cite journal | vauthors = Cohen PA, Goday A, Swann JP | title = The return of rainbow diet pills | journal = American Journal of Public Health | volume = 102 | issue = 9 | pages = 1676–1686 | date = September 2012 | pmid = 22813089 | pmc = 3482033 | doi = 10.2105/AJPH.2012.300655 }}</ref> This was a combination of multiple pills, all thought to help with weight loss, taken throughout the day. Typical regimens included stimulants, such as amphetamines, as well as thyroid hormone, diuretics, digitalis, laxatives, and often a barbiturate to suppress the side effects of the stimulants.<ref name="AJPH2012"/> In 1967/1968 a number of deaths attributed to diet pills triggered a Senate investigation and the gradual implementation of greater restrictions on the market.<ref name=Pool2001/> While rainbow diet pills were banned in the US in the late 1960s, they reappeared in South America and Europe in the 1980s.<ref name="AJPH2012"/> In 1959, phentermine had been FDA approved and fenfluramine in 1973. In the early 1990s two studies found that a combination of the drugs was more effective than either on its own; ''fen-phen'' became popular in the United States and had more than 18 million prescriptions in 1996.<ref>{{cite journal |last1=Setola |first1=Vincent |last2=Roth |first2=Bryan L |title=Screening the receptorome reveals molecular targets responsible for drug-induced side effects: focus on 'fen–phen' |journal=Expert Opinion on Drug Metabolism & Toxicology |date=October 2005 |volume=1 |issue=3 |pages=377–387 |doi=10.1517/17425255.1.3.377|pmid=16863450 |s2cid=30930020 }}</ref> Evidence mounted that the combination could cause valvular heart disease in up to 30 percent of those who had taken it, leading to withdrawal of fen-phen and dexfenfluramine from the market in September 1997.<ref name=Pool2001>{{cite book |last=Pool | first=Robert |title=Fat: Fighting the Obesity Epidemic |publisher=Oxford University Press |location=Oxford, UK |year=2001 |isbn=978-0-19-511853-7 |url-access=registration |url=https://archive.org/details/fatfightingobesi00pool }}</ref>
In the early 2020s, GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy) or tirzepatide (Zepbound) became popular for weight loss because they are more effective than earlier drugs, causing a shortage for patients prescribed these medications for type 2 diabetes, their original indication.<ref>{{cite journal |last1=Lafferty |first1=Ryan A. |last2=Flatt |first2=Peter R. |last3=Irwin |first3=Nigel |title=GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy |journal=Expert Opinion on Pharmacotherapy |date=March 2023 |volume=24 |issue=5 |pages=587–597 |doi=10.1080/14656566.2023.2192865|pmid=36927378 |s2cid=257580812 |doi-access=free }}</ref><ref>{{cite news |title=GLP-1 receptor agonists: Breaking down the hype and demand |url=https://www.pharmacist.com/Publications/Pharmacy-Today/Article/glp-1-receptor-agonists-breaking-down-the-hype-and-demand |access-date=1 November 2023 |work=American Pharmacists Association |archive-date=1 November 2023 |archive-url=https://web.archive.org/web/20231101032838/https://www.pharmacist.com/Publications/Pharmacy-Today/Article/glp-1-receptor-agonists-breaking-down-the-hype-and-demand |url-status=live }}</ref> After the FDA approved semaglutide<ref>{{cite web |title=FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014 |url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014 |archive-url=https://web.archive.org/web/20210604183816/http://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014 |archive-date=4 June 2021 |website=FDA News Release}}</ref> and tirzepatide<ref>{{cite web |title=FDA Approves New Medication for Chronic Weight Management |url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management |archive-url=https://web.archive.org/web/20231108174906/https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management |archive-date=8 November 2023 |website=FDA News Release}}</ref> for chronic weight management, GLP-1 medications became available through various virtual weight loss programs. GLP-1 receptor agonists are associated with reduced riks of cardiovascular events (such as heart attack and stroke) in adults with obesity.<ref name="Elmaleh-Sachs 2023" />
==Patient population== The United States Food and Drug Administration and the European Medicines Agency have approved weight loss medications for adults with either a body-mass index (BMI) of at least 30, or a body-mass index of at least 27 with at least one weight-related comorbidity. This patient population is considered to have sufficiently high baseline health risks to justify the use of anti-obesity medication.<ref>{{cite web |vauthors=Colman E |date=February 2007 |title=Guidance for Industry Developing Products for Weight Management |website=Food and Drug Administration |url=https://www.fda.gov/media/71252/download |access-date=19 July 2022 |archive-date=13 October 2022 |archive-url=https://web.archive.org/web/20221013073226/http://www.fda.gov/media/71252/download }}</ref><ref name=WegovyEMA>{{cite web |title=Wegovy |url=https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy |website=European Medicines Agency |access-date=3 November 2023 |date=11 November 2021 |archive-date=2 July 2022 |archive-url=https://web.archive.org/web/20220702222728/https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy#:~:text=Wegovy%20is%20effective%20at%20reducing,side%20effects%20are%20considered%20manageable. |url-status=live }}</ref><ref name="Elmaleh-Sachs 2023" />
The American Academy of Pediatrics had not previously supported the use of weight loss medication in adolescents but issued new guidelines in 2023, which recommend considering the use of weight loss medication in some overweight children aged 12 or older.<ref>{{cite news |title=A major medical group updated its guidance for treating childhood obesity. Here's what it says. |url=https://www.nbcnews.com/health/kids-health/new-guidelines-treating-childhood-obesity-include-medications-surgery-rcna64651 |access-date=1 November 2023 |work=NBC News |date=9 January 2023 |archive-date=1 November 2023 |archive-url=https://web.archive.org/web/20231101025413/https://www.nbcnews.com/health/kids-health/new-guidelines-treating-childhood-obesity-include-medications-surgery-rcna64651 |url-status=live }}</ref><ref>{{Cite journal |last1=Hampl |first1=Sarah E. |last2=Hassink |first2=Sandra G. |last3=Skinner |first3=Asheley C. |last4=Armstrong |first4=Sarah C. |last5=Barlow |first5=Sarah E. |last6=Bolling |first6=Christopher F. |last7=Avila Edwards |first7=Kimberly C. |last8=Eneli |first8=Ihuoma |last9=Hamre |first9=Robin |date=2023-02-01 |title=Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity |journal=Pediatrics |language=en |volume=151 |issue=2 |article-number=e2022060640 |doi=10.1542/peds.2022-060640 |pmid=36622115 |issn=0031-4005 |doi-access=free}}</ref> The European Medicines Agency has approved semaglutide for children aged 12 or older who have a BMI in the 95 percentile for their age and a weight of at least {{convert|60|kg}}.<ref>{{cite news |title=European Medicines Agency recommends weight loss drug Wegovy for teenagers 12 and up |url=https://www.diabetes.co.uk/news/2023/apr/european-medicines-agency-recommends-weight-loss-drug-wegovy-for-teenagers-12-and-up.html |access-date=1 November 2023 |work=Diabetes |archive-date=1 November 2023 |archive-url=https://web.archive.org/web/20231101025414/https://www.diabetes.co.uk/news/2023/apr/european-medicines-agency-recommends-weight-loss-drug-wegovy-for-teenagers-12-and-up.html |url-status=live }}</ref><ref name=WegovyEMA/> However, GLP-1 agonists may not be cost effective in this population.<ref>{{cite web |title=Latest Obesity Drug Not Cost-Effective for Adolescents |url=https://www.cuimc.columbia.edu/news/latest-obesity-drug-not-cost-effective-adolescents |website=Columbia University Irving Medical Center |access-date=1 November 2023 |date=12 September 2023 |archive-date=1 November 2023 |archive-url=https://web.archive.org/web/20231101025415/https://www.cuimc.columbia.edu/news/latest-obesity-drug-not-cost-effective-adolescents |url-status=live }}</ref>
==Medication==
=== US FDA approved === The US Food and Drug Administration (FDA) approves anti-obesity medications as an adjunctive therapy to diet and exercise for people for whom lifestyle changes do not result in sufficient weight loss. In the United States, semaglutide (Wegovy) is approved by the FDA for chronic weight management.<ref>{{cite press release |date=21 June 2021 |title=FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014 |url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014 |access-date=19 July 2022 |website=U.S. Food and Drug Administration (FDA) |archive-date=4 June 2021 |archive-url=https://web.archive.org/web/20210604235421/https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014 }}</ref> The FDA guidelines say that a therapy may be approved if it results in weight loss that is statistically significant greater than placebo and generally at least five percent of body weight over six months that comes predominantly from fat mass.<ref name=Christoffersen/><ref>{{cite journal |last1=Haslam |first1=D. |title=Weight management in obesity – past and present |journal=International Journal of Clinical Practice |date=March 2016 |volume=70 |issue=3 |pages=206–217 |doi=10.1111/ijcp.12771 |pmid=26811245 |pmc=4832440 |issn=1368-5031}}</ref> Some other prescription weight loss medications are stimulants, which are recommended only for short-term use, and thus are of limited usefulness for patients who may need to reduce weight over months or years.<ref>{{cite web|url=http://emedicine.medscape.com/article/123702-medication|title=Obesity Medication: Gastrointestinal Agents, Other, CNS Stimulants, Anorexiants, Glucagon-like Peptide-1 Agonists, Antidepressants, dopamine reuptake inhibitors; opioid antagonists|website=emedicine.medscape.com|access-date=2 November 2016|archive-date=4 November 2016|archive-url=https://web.archive.org/web/20161104011650/http://emedicine.medscape.com/article/123702-medication|url-status=live}}</ref> As of 2022, there is no pathway for approval for drugs that reduce fat mass without 5 percent overall weight loss, even if they significantly improve metabolic health; neither is there one for drugs that help patients maintain weight loss although this can be more challenging than losing weight.<ref name=Christoffersen/>
As of 2022, no medication has been discovered that would equal the effectiveness of bariatric surgery for long-term weight loss and improved health outcomes.<ref name="pmid34815532">{{cite journal |last1=Müller |first1=Timo D. |last2=Blüher |first2=Matthias |last3=Tschöp |first3=Matthias H. |last4=DiMarchi |first4=Richard D. |title=Anti-obesity drug discovery: advances and challenges |journal=Nature Reviews Drug Discovery |date=March 2022 |volume=21 |issue=3 |pages=201–223 |doi=10.1038/s41573-021-00337-8 |pmid=34815532 |pmc=8609996 }}</ref>
In 2026, oral GLP-1 medications for obesity reached the market, serving as a more convenient alternative to traditional injections. In December 2025, the FDA approved an oral formulation of semaglutide (Wegovy) from Novo Nordisk.{{cite web |title=FDA Approves Oral Semaglutide as First GLP-1 Pill for Weight Loss |url=https://www.ajmc.com/view/fda-approves-oral-semaglutide-as-first-glp-1-pill-for-weight-loss |access-date=2026-04-14 |website=AJMC}} On April 1, 2026, the FDA approved orforglipron (Foundayo), manufactured by Eli Lilly, as a once-daily oral GLP-1 receptor agonist for weight management. It is the first oral GLP-1 that can be taken at any time of day without food or water restrictions.{{cite web |title=FDA Approves First New Molecular Entity Under National Priority Voucher Program |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-new-molecular-entity-under-national-priority-voucher-program |access-date=2026-04-14 |website=U.S. Food and Drug Administration}} {| class="wikitable" |+ !Medication Name !Trade name(s) !Mechanism of action !Current FDA Status !placebo-adjusted percent bodyweight lost (highest dose studied) |- |Semaglutide |Wegovy, Ozempic |GLP-1 receptor agonist |Approved for weight management (chronic) |12%<ref name="Once-Weekly Semaglutide in Adults w">{{cite journal | vauthors = Wilding JP, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MT, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF | title = Once-Weekly Semaglutide in Adults with Overweight or Obesity | journal = The New England Journal of Medicine | volume = 384 | issue = 11 | pages = 989–1002 | date = March 2021 | pmid = 33567185 | doi = 10.1056/NEJMoa2032183 | s2cid = 231883214 | url = https://discovery.ucl.ac.uk/id/eprint/10127569/ | access-date = 21 February 2023 | archive-date = 18 March 2023 | archive-url = https://web.archive.org/web/20230318145219/https://discovery.ucl.ac.uk/id/eprint/10127569/ | url-status = live | doi-access = free }}</ref> |- |Phentermine/topiramate |Qsymia |Phentermine is a substituted amphetamine and topiramate has an unknown mechanism of action |Approved for weight management (short-term) by the FDA but not the European Medicines Agency<ref>{{cite web |date=13 June 2013 |title=Qsiva |url=https://www.ema.europa.eu/en/medicines/human/EPAR/qsiva |website=European Medicines Agency (EMA) |access-date=12 December 2022 |archive-date=12 December 2022 |archive-url=https://web.archive.org/web/20221212222154/https://www.ema.europa.eu/en/medicines/human/EPAR/qsiva |url-status=live }}</ref> |10%<ref>{{cite journal | vauthors = Smith SM, Meyer M, Trinkley KE | title = Phentermine/topiramate for the treatment of obesity | journal = The Annals of Pharmacotherapy | volume = 47 | issue = 3 | pages = 340–349 | date = March 2013 | pmid = 23482732 | doi = 10.1345/aph.1R501 | s2cid = 30461611 }}</ref> or {{convert|8.25| kg}}<ref>{{cite journal |last1=Lei |first1=Xiang-Guo |last2=Ruan |first2=Jia-Qi |last3=Lai |first3=Chen |last4=Sun |first4=Ziyi |last5=Yang |first5=Xi |title=Efficacy and Safety of Phentermine/Topiramate in Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis |journal=Obesity |date=June 2021 |volume=29 |issue=6 |pages=985–994 |doi=10.1002/oby.23152 |pmid=33864346 |s2cid=233278420 }}</ref> |- |Naltrexone/bupropion |Contrave |Reduces food cravings by inhibiting the mesolimbic system via activation of proopiomelanocortin neurons in the hypothalamus.<ref name="Elmaleh-Sachs 2023" /> |Approved for weight management (chronic) in the US and EU<ref name="Mysimba EPAR">{{cite web | title=Mysimba EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/mysimba | access-date=5 August 2020 | archive-date=22 October 2020 | archive-url=https://web.archive.org/web/20201022220427/https://www.ema.europa.eu/en/medicines/human/EPAR/mysimba | url-status=live }}</ref> |5 percent<ref name="ncbi.nlm.nih.gov"/> |- |Liraglutide |Saxenda |GLP-1 receptor agonist |Approved for weight management (chronic) |4 percent<ref>{{cite journal |last1=Alruwaili |first1=Heshma |last2=Dehestani |first2=Babak |last3=le Roux |first3=Carel W |title=Clinical Impact of Liraglutide as a Treatment of Obesity |journal=Clinical Pharmacology: Advances and Applications |date=March 2021 |volume= 13 |pages=53–60 |doi=10.2147/CPAA.S276085 |pmid=33732030 |pmc=7958997 |issn=1179-1438 |doi-access=free }}</ref> |- |Gelesis100 (medical device) |Plenity |Oral hydrogel |FDA approved for weight management (chronic) but the American Gastroenterology Association recommends that its use be limited to clinical trials due to lack of evidence.<ref name=AGA_Obesity_Guidelines_2022>{{cite journal |last1=Grunvald |first1=E |last2=Shah |first2=R |last3=Hernaez |first3=R |last4=Chandar |first4=AK |last5=Pickett-Blakely |first5=O |last6=Teigen |first6=LM |last7=Harindhanavudhi |first7=T |last8=Sultan |first8=S |last9=Singh |first9=S |last10=Davitkov |first10=P |last11=AGA Clinical Guidelines |first11=Committee |title=AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. |journal=Gastroenterology |date=November 2022 |volume=163 |issue=5 |pages=1198–1225 |doi=10.1053/j.gastro.2022.08.045 |pmid=36273831|s2cid=253052479 |doi-access=free }}</ref> |2%<ref>{{cite journal | vauthors = Greenway FL, Aronne LJ, Raben A, Astrup A, Apovian CM, Hill JO, Kaplan LM, Fujioka K, Matejkova E, Svacina S, Luzi L, Gnessi L, Navas-Carretero S, Alfredo Martinez J, Still CD, Sannino A, Saponaro C, Demitri C, Urban LE, Leider H, Chiquette E, Ron ES, Zohar Y, Heshmati HM | title = A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss | journal = Obesity | volume = 27 | issue = 2 | pages = 205–216 | date = February 2019 | pmid = 30421844 | pmc = 6587502 | doi = 10.1002/oby.22347 }}</ref> |- |Orlistat |Xenical |Absorption inhibitor |Approved for weight management (chronic) |{{convert|3|kg}}; percentage not provided<ref>{{cite journal | vauthors = Padwal RS, Majumdar SR | title = Drug treatments for obesity: orlistat, sibutramine, and rimonabant | journal = Lancet | volume = 369 | issue = 9555 | pages = 71–77 | date = January 2007 | pmid = 17208644 | doi = 10.1016/S0140-6736(07)60033-6 | s2cid = 35104831 }}</ref> |- |Phentermine |Adipex |Substituted amphetamine |Approved for weight management (short-term) |{{convert|5|kg}}<ref>{{cite journal |last1=Kim |first1=Kyoung Kon |last2=Cho |first2=Hi-Jung |last3=Kang |first3=Hee-Cheol |last4=Youn |first4=Bang-Bu |last5=Lee |first5=Kyu-Rae |title=Effects on Weight Reduction and Safety of Short-Term Phentermine Administration in Korean Obese People |journal=Yonsei Medical Journal |date=October 2006 |volume=47 |issue=5 |pages=614–625 |doi=10.3349/ymj.2006.47.5.614 |pmid=17066505 |pmc=2687747 |issn=0513-5796}}</ref> |- |Tirzepatide |Mounjaro/ Zepbound |Dual GLP-1 receptor agonist and GIP agonist |Approved for weight management (chronic)<ref name=zepboundapproval>{{cite web |date=8 November 2023 |title=FDA Approves Lilly's Zepbound™ (tirzepatide) for Chronic Weight Management, a Powerful New Option for the Treatment of Obesity or Overweight with Weight-Related Medical Problems |url=https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-zepboundtm-tirzepatide-chronic-weight |access-date=13 November 2023 |website=investor.lilly.com/ |archive-date=13 November 2023 |archive-url=https://web.archive.org/web/20231113065428/https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-zepboundtm-tirzepatide-chronic-weight |url-status=live }}</ref> |18.4 percent<ref>{{Cite journal |last1=Wadden |first1=Thomas A |last2=Chao |first2=Ariana M |last3=Machineni |first3=Sriram |last4=Kushner |first4=Robert |last5=Ard |first5=Jamy |last6=Srivastava |first6=Gitanjali |last7=Halpern |first7=Bruno |last8=Zhang |first8=Shuyu |last9=Chen |first9=Jiaxun |last10=Bunck |first10=Mathijs C |last11=Ahmad |first11=Nadia N |last12=Forrester |first12=Tammy |date=2023-10-15 |title=Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial |journal=Nature Medicine |language=en |volume=29 |issue=11 |pages=2909–2918 |doi=10.1038/s41591-023-02597-w |pmid=37840095 |pmc=10667099 }}</ref> |}
===Withdrawn===
{| class="wikitable" |+ !Medication Name !Trade name(s) !Mechanism of action !Current FDA Status !placebo-adjusted percent bodyweight lost (highest dose studied) |- |Lorcaserin |Belviq |5-HT2C receptor agonist |Withdrawn for safety reasons | 6.25 percent<ref>{{cite journal |last1=Tuccinardi |first1=Dario |last2=Farr |first2=Olivia M. |last3=Upadhyay |first3=Jagriti |last4=Oussaada |first4=Sabrina M. |last5=Mathew |first5=Hannah |last6=Paschou |first6=Stavroula A. |last7=Perakakis |first7=Nikolaos |last8=Koniaris |first8=Anastasia |last9=Kelesidis |first9=Theodoros |last10=Mantzoros |first10=Christos S. |title=Lorcaserin treatment decreases body weight and improves cardiometabolic risk factors of obese adults: A 6-month-long, randomized, placebo-controlled, double-blind clinical trial. |journal=Diabetes, Obesity & Metabolism |date=June 2019 |volume=21 |issue=6 |pages=1487–1492 |doi=10.1111/dom.13655 |pmid=30724455 |pmc=6504613 |issn=1462-8902}}</ref> |- |Sibutramine |Meridia |Serotonin–norepinephrine reuptake inhibitor |Withdrawn due to cardiovascular risks<ref name=Meridia2010>{{cite web|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm|title=Meridia (sibutramine): Market Withdrawal Due to Risk of Serious Cardiovascular Events|website=Food and Drug Administration |access-date=16 December 2019|archive-date=18 January 2017|archive-url=https://web.archive.org/web/20170118093659/http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm228830.htm}}</ref><ref>{{cite web |date=23 October 2012 |title=Recalls and safety alerts |url=https://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2010/10058r-eng.php |url-status=live |archive-url=https://web.archive.org/web/20201023051149/https://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2010/10058r-eng.php |archive-date=23 October 2020 |access-date=31 August 2020 |work=Health Canada |publisher=Government of Canada}}</ref> | 19.7 percent<ref>{{cite journal |last1=Dedov |first1=Ivan Ivanovich |last2=Melnichenko |first2=Galina Afanasievna |last3=Troshina |first3=Ekaterina Anatolievna |last4=Mazurina |first4=Natalya Valentinovna |last5=Galieva |first5=Marina Olegovna |title=Body Weight Reduction Associated with the Sibutramine Treatment: Overall Results of the PRIMAVERA Primary Health Care Trial |journal=Obesity Facts |date=September 2018 |volume=11 |issue=4 |pages=335–343 |doi=10.1159/000488880 |pmid=30089303 |pmc=6189539 |issn=1662-4025}}</ref> |- |Rimonabant |Acomplia, Zimulti |Cannabinoid receptor antagonist |Withdrawn for safety reasons | {{convert|2.6 to 6.3|kg}}<ref>{{cite journal |last1=Christopoulou |first1=F. D. |last2=Kiortsis |first2=D. N. |title=An overview of the metabolic effects of rimonabant in randomized controlled trials: potential for other cannabinoid 1 receptor blockers in obesity: The metabolic effects of rimonabant |journal=Journal of Clinical Pharmacy and Therapeutics |date=February 2011 |volume=36 |issue=1 |pages=10–18 |doi=10.1111/j.1365-2710.2010.01164.x |pmid=21198716 |s2cid=3274949 |doi-access=free }}</ref> |- |Fenfluramine |Fintepla, Pondimin |Serotonin releasing agent |Withdrawn for safety reasons | - |- |Fenfluramine/phentermine (fen-phen) |Pondimin | |Withdrawn for safety reasons |13.9 percent<ref>{{cite journal |last1=Wadden |first1=T. A. |last2=Berkowitz |first2=R. I. |last3=Silvestry |first3=F. |last4=Vogt |first4=R. A. |last5=St John Sutton |first5=M. G. |last6=Stunkard |first6=A. J. |last7=Foster |first7=G. D. |last8=Aber |first8=J. L. |title=The fen-phen finale: a study of weight loss and valvular heart disease |journal=Obesity Research |date=July 1998 |volume=6 |issue=4 |pages=278–284 |doi=10.1002/j.1550-8528.1998.tb00350.x |pmid=9688104 |issn=1071-7323|doi-access=free }}</ref> |- |Dexfenfluramine |Redux |Serotonin releasing agent |Withdrawn for safety reasons |{{convert|3.5|kg}}<ref>{{cite journal |last1=Davis |first1=Rick |last2=Faulds |first2=Diana |title=Dexfenfluramine |journal=Drugs |date=November 1996 |volume=52 |issue=5 |pages=696–724 |doi=10.2165/00003495-199652050-00007 |pmid=9118819 |s2cid=195698330 }}</ref> |- |2,4-Dinitrophenol | |Uncoupling agent |Withdrawn for safety reasons |{{convert|17.1|lb}} per patient on average (uncontrolled study)<ref>{{cite journal |last1=Tainter |first1=M. L. |title=Dinitrophenol in the Treatment of Obesity: Final Report |journal=Journal of the American Medical Association |date=August 1935 |volume=105 |issue=5 |page=332 |doi=10.1001/jama.1935.02760310006002}}</ref>
|- | Ephedrine | | Adrenergic agonist | Approved for asthma<ref>{{cite web |title=Role of OTC Asthma Medications in the Community Pharmacy |url=https://www.pharmacytimes.com/view/role-of-otc-asthma-medications-in-the-community-pharmacy |website=Pharmacy Times |access-date=24 October 2023 |date=8 December 2021 |archive-date=19 February 2023 |archive-url=https://web.archive.org/web/20230219010658/https://www.pharmacytimes.com/view/role-of-otc-asthma-medications-in-the-community-pharmacy |url-status=live }}</ref> |Average of {{convert|1.9|kg}} in a meta-analysis (all dosages)<ref>{{cite journal |last1=Yoo |first1=Hee-Jeong |last2=Yoon |first2=Ha-Young |last3=Yee |first3=Jeong |last4=Gwak |first4=Hye-Sun |title=Effects of Ephedrine-Containing Products on Weight Loss and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |journal=Pharmaceuticals |date=November 2021 |volume=14 |issue=11 |page=1198 |doi=10.3390/ph14111198 |pmid=34832979 |pmc=8618781 |issn=1424-8247 |doi-access=free }}</ref> |- |ECA stack | |Combination of ephedrine and caffeine, sometimes adding aspirin | |Around {{convert|4-6|kg}}<ref name=Eckerson/> |- |Ephedra |Plant extract sold as a dietary supplement |Contains ephedrine, an adrenergic agonist |Banned in 2004 for safety reasons |{{convert|0.9|kg}} per month more than placebo<ref name=Eckerson>{{cite book |last1=Eckerson |first1=Joan M. |title=Nutritional Supplements in Sports and Exercise |date=2015 |publisher=Springer International Publishing |isbn=978-3-319-18230-8 |pages=159–185 |chapter-url=https://link.springer.com/chapter/10.1007/978-3-319-18230-8_8 |chapter=Weight Loss Nutritional Supplements |doi=10.1007/978-3-319-18230-8_8 |access-date=24 October 2023 |archive-date=2 November 2023 |archive-url=https://web.archive.org/web/20231102060326/https://link.springer.com/chapter/10.1007/978-3-319-18230-8_8 |url-status=live }}</ref> |- |Amphetamine salts |Obetrol | |Approved 1960, withdrawn 1973; Adderall was later approved for ADHD and narcolepsy and is still used for those purposes | |- |Phenylpropanolamine |Was an over-the-counter medication ingredient | |Withdrawn in 2005 due to risk of hemorragic stroke |{{convert|1.5|kg}}<ref>{{cite journal |last1=Schteingart |first1=D. E. |title=Effectiveness of phenylpropanolamine in the management of moderate obesity |journal=International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity |date=July 1992 |volume=16 |issue=7 |pages=487–493 |pmid=1323545 }}</ref> |}
===Never approved or not currently approved===
{| class="wikitable" |+ !Medication Name !Trade name(s) !Mechanism of action !Current FDA Status !placebo-adjusted percent bodyweight lost (highest dose studied) |- |Retatrutide | |GLP-1, GIP, and glucagon receptor triple agonist |In clinical trials |24 percent in a Phase II trial<ref>{{cite journal | vauthors = Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML | title = Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial | journal = The New England Journal of Medicine | date = June 2023 | volume = 389 | issue = 6 | pages = 514–526 | pmid = 37366315 | doi = 10.1056/NEJMoa2301972| s2cid = 259260926 }} Free access subject to registration.</ref> |- |UBT251 | |GLP-1, GIP, and glucagon receptor triple agonist |In clinical trials |19.7% in a Phase II trial<ref>{{Cite web |last=Taylor |first=Nick Paul |date=2026-02-24 |title=Novo's triple G candidate drives 20% weight loss in phase 2 |url=https://www.fiercebiotech.com/biotech/novo-nordisks-triple-g-candidate-drives-20-weight-loss-phase-2-china |access-date=2026-03-05 |website=www.fiercebiotech.com |language=en}}</ref><ref>{{Cite web |last=Beaney |first=Abigail |date=2026-02-25 |title=Novo Nordisk-partnered drug shows 19.7% weight loss in Phase II trial |url=https://www.clinicaltrialsarena.com/news/novo-nordisk-partnered-drug-shows-19-7-weight-loss-in-phase-ii-trial/ |access-date=2026-03-05 |website=Clinical Trials Arena |language=en-US}}</ref> |- |Exenatide |Byetta |GLP-1 receptor agonist |Approved for type 2 diabetes |{{convert|2.5|kg}}<ref>{{cite journal |last1=Dushay |first1=Jody |last2=Gao |first2=Chuanyun |last3=Gopalakrishnan |first3=Gosala S. |last4=Crawley |first4=Meghan |last5=Mitten |first5=Emilie K. |last6=Wilker |first6=Elissa |last7=Mullington |first7=Janet |last8=Maratos-Flier |first8=Eleftheria |title=Short-Term Exenatide Treatment Leads to Significant Weight Loss in a Subset of Obese Women Without Diabetes |journal=Diabetes Care |date=January 2012 |volume=35 |issue=1 |pages=4–11 |doi=10.2337/dc11-0931 |pmid=22040840 |pmc=3241299 |issn=0149-5992}}</ref> |- |Cetilistat | |Absorption inhibitor |Not approved | {{convert|1.5|kg}}<ref>{{cite journal |last1=Kopelman |first1=Peter |last2=Groot |first2=Gerrit de H. |last3=Rissanen |first3=Aila |last4=Rossner |first4=Stephan |last5=Toubro |first5=Soren |last6=Palmer |first6=Richard |last7=Hallam |first7=Rob |last8=Bryson |first8=Andrew |last9=Hickling |first9=Roger I. |title=Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical) |journal=Obesity (Silver Spring) |date=January 2010 |volume=18 |issue=1 |pages=108–115 |doi=10.1038/oby.2009.155 |pmid=19461584 |s2cid=205526626 }}</ref> |- | Tesofensine (NS2330) | |Serotonin–norepinephrine–dopamine reuptake inhibitor |Not FDA approved |10.6 percent<ref>{{cite journal |last1=Axel |first1=Anne Marie D |last2=Mikkelsen |first2=Jens D |last3=Hansen |first3=Henrik H |title=Tesofensine, a Novel Triple Monoamine Reuptake Inhibitor, Induces Appetite Suppression by Indirect Stimulation of α1 Adrenoceptor and Dopamine D1 Receptor Pathways in the Diet-Induced Obese Rat |journal=Neuropsychopharmacology |date=June 2010 |volume=35 |issue=7 |pages=1464–1476 |doi=10.1038/npp.2010.16 |pmid=20200509 |pmc=3055463 |issn=0893-133X}}</ref>
|- |Metformin |Glucophage |Unknown |Approved for type 2 diabetes |5.6 percent<ref>{{cite journal |last1=Seifarth |first1=C. |last2=Schehler |first2=B. |last3=Schneider |first3=H. J. |title=Effectiveness of metformin on weight loss in non-diabetic individuals with obesity |journal=Experimental and Clinical Endocrinology & Diabetes |date=January 2013 |volume=121 |issue=1 |pages=27–31 |doi=10.1055/s-0032-1327734 |pmid=23147210 |s2cid=20506527 |issn=1439-3646|doi-access=free }}</ref> |- |Cagrilintide | |Dual amylin and calcitonin receptor agonist (DACRA) |Not approved |7.8 percent<ref>{{cite journal |last1=Lau |first1=David C W |last2=Erichsen |first2=Lars |last3=Francisco |first3=Ann Marie |last4=Satylganova |first4=Altynai |last5=le Roux |first5=Carel W |last6=McGowan |first6=Barbara |last7=Pedersen |first7=Sue D |last8=Pietiläinen |first8=Kirsi H |last9=Rubino |first9=Domenica |last10=Batterham |first10=Rachel L |title=Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial |journal=The Lancet |date=December 2021 |volume=398 |issue=10317 |pages=2160–2172 |doi=10.1016/S0140-6736(21)01751-7 |pmid=34798060 |s2cid=244169045 |url=https://discovery.ucl.ac.uk/id/eprint/10155031/ }}</ref> |- |Cagrilintide/semaglutide |CagriSema |DACRA/GLP-1 agonist combination |Not approved |20.4 percent in phase III trial<ref>{{Cite journal |last1=Garvey |first1=W. Timothy |last2=Blüher |first2=Matthias |last3=Contreras |first3=Cynthia Karenina Osorto |last4=Davies |first4=Melanie J. |last5=Lehmann |first5=Eva Winning |last6=Pietiläinen |first6=Kirsi H. |last7=Rubino |first7=Domenica |last8=Sbraccia |first8=Paolo |last9=Wadden |first9=Thomas |last10=Zeuthen |first10=Niels |last11=Wilding |first11=John P. H. |title=Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity |url=https://www.nejm.org/doi/full/10.1056/NEJMoa2502081 |journal=New England Journal of Medicine |date=2025 |issue=7 |pages=635–647 |volume=393 |doi=10.1056/NEJMoa2502081 |pmid=40544433 |issn=0028-4793|url-access=subscription }}</ref> |- |VK2735 | |Dual GLP-1 and GIP receptor agonist |In Phase 3 clinical trials |14.7% in a Phase II trial.<ref>{{cite journal |last1=Bays |first1=Harold E. |last2=Toth |first2=Phillip |last3=Alkhouri |first3=Naim |last4=Pullman |first4=John |last5=Freilich |first5=Bradley |last6=Neutel |first6=Joel |last7=Ji |first7=Summer |last8=Stubbe |first8=Scott |last9=Hedges |first9=Parke |last10=Lian |first10=Brian |date=January 8, 2026 |title=Weekly Subcutaneous VK2735, a GIP/GLP-1 Receptor Dual Agonist, for Weight Management: Phase 2, Randomized, 13-Week VENTURE Study |journal=Obesity |doi=10.1002/oby.70106 |url=https://onlinelibrary.wiley.com/doi/10.1002/oby.70106 |access-date=March 29, 2026|pmc=12933218 }}</ref> |- |Survodutide | |Dual GLP-1 and GIP receptor agonist |In Phase 3 clinical trials |16.6% in a Phase III trial.<ref>{{Cite web |last=Look |first=Aimee |date=2026-04-28 |title=Boehringer Ingelheim’s Obesity Drug Helps Lose Fat Rather Than Muscle, Late-Stage Trial Shows |url=https://www.wsj.com/health/pharma/boehringer-ingelheims-obesity-drug-helps-lose-fat-rather-than-muscle-late-stage-trial-shows-41ad98ea |access-date=2026-04-28 |website=The Wall Street Journal |language=en-US}}</ref> |}
==Safety and side effects== Some anti-obesity medications can have severe, even lethal side effects, fen-phen being a famous example. Fen-phen was reported through the FDA to cause abnormal echocardiograms, heart valve problems, and rare valvular diseases.<ref>{{cite web| vauthors = Bachorik L |title=FDA Announces Withdrawal Fenfluramine and Dexfenfluramine (Fen-Phen) |url= https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm179871.htm |work=U.S. Food and Drug Administration |publisher=U.S. Food and Drug Administration (FDA)|access-date=27 January 2014|archive-date=4 November 2009|archive-url=https://web.archive.org/web/20091104225047/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm179871.htm}}</ref> Out of 25 anti-obesity medications withdrawn from the market between 1964 and 2009, 23 acted by altering the functions of chemical neurotransmitters in the brain. The most common side effects of these drugs that led to withdrawals were mental disturbances, cardiac side effects, and drug abuse or drug dependence. Deaths were associated with seven products.<ref>{{cite journal |last1=Onakpoya |first1=Igho J. |last2=Heneghan |first2=Carl J. |last3=Aronson |first3=Jeffrey K. |date=2016 |title=Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review |journal=BMC Medicine |volume=14 |issue=1 |page=191 |doi=10.1186/s12916-016-0735-y |issn=1741-7015 |pmc=5126837 |pmid=27894343 |doi-access=free }}</ref> Ephedra was removed from the US market in 2004 over concerns that it raises blood pressure and could lead to strokes and death.<ref name=Kolata2007>{{cite book |last=Kolata | first=Gina |title=Rethinking thin: The new science of weight loss – and the myths and realities of dieting |publisher=Picador |year=2007 |isbn=978-0-312-42785-6}}</ref>
=== Weight regain === Weight regain is common upon discontinuation of weight loss medications, and long-term therapy may sometimes be required for sustained weight loss.<ref name="Elmaleh-Sachs 2023" /> After stopping treatment with GLP-1 agonists such as semaglutide, liraglutide and tirzepatide, people regain on average more than half (50–70%) of the lost weight within 1 year.<ref>{{Cite journal |last1=McGowan |first1=Barbara |last2=Ciudin |first2=Andreea |last3=Baker |first3=Jennifer L. |last4=Busetto |first4=Luca |last5=Dicker |first5=Dror |last6=Frühbeck |first6=Gema |last7=Goossens |first7=Gijs H. |last8=Monami |first8=Matteo |last9=Sbraccia |first9=Paolo |date=2025-10-02 |title=A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults |journal=Nature Medicine |language=en |pages=1–13 |doi=10.1038/s41591-025-03978-z |pmid=41039116 |issn=1546-170X |doi-access=free|pmc=12532627 }}</ref><ref>{{Cite journal |last1=Quarenghi |first1=Massimo |last2=Capelli |first2=Silvia |last3=Galligani |first3=Giulia |last4=Giana |first4=Arianna |last5=Preatoni |first5=Giorgia |last6=Turri Quarenghi |first6=Rosamaria |date=2025-05-28 |title=Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption: A Narrative Review of Randomized Studies |journal=Journal of Clinical Medicine |volume=14 |issue=11 |page=3791 |doi=10.3390/jcm14113791 |doi-access=free |issn=2077-0383 |pmc=12155999 |pmid=40507553}}</ref>
People return to their previous weight within a year and a half after stopping anti-obesity medications.<ref>{{Cite journal |last1=West |first1=Sam |last2=Scragg |first2=Jadine |last3=Aveyard |first3=Paul |last4=Oke |first4=Jason L. |last5=Willis |first5=Lia |last6=Haffner |first6=Stella J. P. |last7=Knight |first7=Heather |last8=Wang |first8=Danni |last9=Morrow |first9=Sarah |last10=Heath |first10=Laura |last11=Jebb |first11=Susan A. |last12=Koutoukidis |first12=Dimitrios A. |date=2026-01-07 |title=Weight regain after cessation of medication for weight management: systematic review and meta-analysis |journal=BMJ |volume=392 |article-number=e085304 |doi=10.1136/bmj-2025-085304 |issn=1756-1833 |pmc=12776922 |pmid=41500720 |doi-access=free}}</ref>
== References == {{reflist}}
== External links == * {{Commons category-inline}} * [https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity Prescription Medications to Treat Overweight & Obesity] US National Institute of Diabetes and Digestive and Kidney Diseases
{{Obesity}} {{Antiobesity preparations}} {{Major drug groups}} {{Portal bar | Medicine}} {{Authority control}}
{{DEFAULTSORT:Anti-Obesity Medication}} Category:Anti-obesity drugs